EsketamineSPRAVATO
Treatment of treatment-resistant depression (major depressive disorder) in adults who have not responded adequately to at least two separate courses of treatment with different antidepressants, each of adequate dose and duration, in the current moderate to severe depressive episode.
Decisions on record
- Meeting Dec 2024 Recommended Treatment-resistant major depression in patients who have failed at least two prior oral anti-depressant drugs no PSD
- Meeting Jul 2024 Deferred Treatment-resistant depression
- Meeting Jul 2023 Not recommended Treatment resistant depression (TRD)
- Meeting Jul 2022 Not recommended Treatment-resistant depression in patients who have failed at least two prior oral antidepressants
- Meeting Jul 2021 Not recommended Treatment-resistant depression
Access path
- TGA registered · SPRAVATO
TGA label narrower than the PBS population
- Jul 2021Not recommended
Positioned inappropriately early in treatment algorithm; comparator not clinically appropriate (requirement to commence…
- Jul 2022Not recommended
Comparator changed: newly prescribed oral antidepressant alone → newly initiated oral…
- Jul 2023Not recommended
Comparator changed: newly initiated oral antidepressant (OAD) alone → newly initiated…
- ↻ resubmittedDec 2024Recommended · restricted
Comparator changed: newly initiated oral antidepressant alone → newly initiated oral…
- PBS listing · Authority Required
From the public summary
7.1 The PBAC deferred making a recommendation for the listing of esketamine for the treatment of treatment-resistant depression (TRD) in patients who have failed two or more prior oral anti-depressant drugs (OADs). The PBAC reiterated its previous consideration that, based on the available clinical evidence, esketamine was likely to be effective for some patients.PSD · Jul 2024
7.2 The PBAC noted the input from healthcare professionals and individuals supported the listing of esketamine and described it as an effective and well-tolerated treatment, with patients who respond experiencing a rapid and life-changing impact on symptoms and quality of life. The Committee recalled the input from clinicians and individuals in previous considerations of esketamine described similar benefits from esketamine treatment.PSD · Jul 2024
6.52 The resubmission presented a stepped economic evaluation of esketamine nasal spray plus a newly initiated OAD versus a newly initiated OAD alone in patients with moderate to severe TRD. The economic analysis was based on evidence from the TRANSFORM-2, TRANSFORM-3 and SUSTAIN-1 trials, as well as additional modelled variables. The economic evaluation was presented as a cost-utility analysis.PSD · Jul 2024
6.53 The key changes to the economic evaluation in the current resubmission compared with the July 2023 submission include:PSD · Jul 2024
6.46 The clinical claim for the resubmission remained the same as the July 2023 resubmission, that is: esketamine nasal spray in combination with a newly initiated OAD is superior in terms of effectiveness and inferior in terms of safety, compared with a newly initiated OAD alone.PSD · Jul 2024
6.47 The PBAC previously considered that the claim of superior comparative effectiveness may be reasonable, although the magnitude and clinical importance of the observed benefits was uncertain (para 7.10, esketamine PSD, July 2023 PBAC meeting). The PBAC previously considered the claim of non-inferior safety was reasonable, however remained concerned there was limited longer-term safety data.PSD · Jul 2024
6.2 The PBAC noted and welcomed the input from individuals (2), health care professionals (17) and organisations (1) via the Consumer Comments facility on the PBS website. The comments described a range of benefits of treatment with esketamine including rapid improvement in mood, good remission rates, reduction in suicidal ideation and reduction in hospital admissions.PSD · Jul 2024
6.3 Individuals living with TRD described the impact of TRD on every facet of daily life and the enduring feelings of despair, worthlessness and hopelessness that come with it.PSD · Jul 2024
Cost-effectiveness
ICER values are redacted/commercially sensitive; the document does not publish numeric ICER figures
Decision context
PopulationAdults aged 18 years or older with major depressive disorder who have not responded adequately to at least two separate courses of treatment with different antidepressants (from different pharmacological classes) of adequate dose and duration in the current moderate to severe depressive episode, treated in conjunction with a newly initiated (or concomitant) oral antidepressant under supervision of a healthcare professional.
Risk sharingRisk-sharing arrangement with a higher rebate percentage for any use above the subsidisation caps
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Dec 2024 | Recommended · restricted | newly initiated oral antidepressant | — | RCT · Other |
| Jul 2023 | Not recommended | newly initiated oral antidepressant alone | — | RCT · Change in depression severity |
| Jul 2022 | Not recommended | newly initiated oral antidepressant (OAD) alone | — | RCT · Change in depression severity (MADRS total score), clinical response and remission |
| Jul 2021 | Not recommended | newly prescribed oral antidepressant alone | — | RCT · Change in depression severity (MADRS total score), clinical response and remission |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| ASPIRE-1 | NA | 102 | NRMS | recruiting |
| TRANSFORM-2 | Ph 3 | 236 | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score up t… | completed |
| TRANSFORM-3 | Ph 3 | 139 | Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score up t… | completed |
| SUSTAIN-1 | Ph 3 | 719 | Time to Relapse in Participants With Stable Remission (Maintenance Phase) | completed |
Consumer voice
Individuals and healthcare professionals reported that esketamine provides rapid improvement in mood, good remission rates, and reduction in suicidal ideation, offering hope to patients where other treatments have failed. However, affordability and access remain significant barriers to treatment.
The comments described a range of benefits of treatment with esketamine including rapid improvement in mood, good remission rates, reduction in suicidal ideation and reduction in hospital admissions. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to antidepressants from different pharmacological classes; TGA label does not specify this requirement.